期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 218, 期 10, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20210724
关键词
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资金
- National Institutes of Health [GM24417-40]
- Huong Hoa District Health Center
The coadministration of imatinib with standard of care (SOC) in uncomplicated P. falciparum malaria patients led to a faster decline in parasite density and fever, without any delayed parasite clearance. The improvements were most significant in patients with the highest parasite density, where serious complications and death are most common.
To egress from its erythrocyte host, the malaria parasite, Plasmodium falciparum, must destabilize the erythrocyte membrane by activating an erythrocyte tyrosine kinase. Because imatinib inhibits erythrocyte tyrosine kinases and because imatinib has a good safety profile, we elected to determine whether coadministration of imatinib with standard of care (SOC) might be both well tolerated and therapeutically efficacious in malaria patients. Patients with uncomplicated P. falciparum malaria from a region in Vietnam where one third of patients experience delayed parasite clearance (DPC; continued parasitemia after 3 d of therapy) were treated for 3 d with either the region's SOC (40 mg dihydroartemisinin + 320 mg piperaquine/d) or imatinib (400 mg/d) + SOC. Imatinib + SOC-treated participants exhibited no increase in number or severity of adverse events, a significantly accelerated decline in parasite density and pyrexia, and no DPC. Surprisingly, these improvements were most pronounced in patients with the highest parasite density, where serious complications and death are most frequent. Imatinib therefore appears to improve SOC therapy, with no obvious drug-related toxicities.
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